A comparison of angina symptoms reported by clinicians and patients, pre and post revascularisation: Insights from the Stent or Surgery Trial.

BACKGROUND: There are limited data comparing the consistency of angina reporting by patients and clinicians. METHODS: We performed a retrospective analysis of data from the randomised Stent or Surgery (SoS) trial. The trial required reporting of angina using the Canadian Cardiovascular Society (CCS) classification by both patients and clinicians at baseline and twelve months. We compared paired observations to describe the magnitude and direction of differences in clinician and patient reporting. The difference in CCS grade was expressed as the clinician minus patient value. We also examined the proportion of trial subjects reported as being free from angina (CCS = 0) in clinician and patient reporting. RESULTS: Paired CCS data was available for 912 and 887 cases at baseline and 12 months respectively. At baseline, clinicians reported freedom from angina in a single case (1/912 = 0.1%) compared to 70/912 (7.7%) patients (Delta 7.6% 95% CI 5.8 to 9.3, P ≤0.001). At 12 months, the position was reversed, with clinicians reporting 639/887 (72%) angina free compared to 449/887 (50.6%) for patients (Delta -21.4 95% CI -17.1 to -25.8 P ≤ 0.001). For the reported CCS grade at follow-up, the weighted linear kappa for overall agreement was 0.312. Discordant reporting involved the clinician suggesting less angina rather than more (36% v 8% of cases). CONCLUSIONS: These findings have implications for our perception of previous research which has, in the main, focussed on clinician reporting. This emphasises the importance of patient reporting and a need to better understand reasons for discordance.

Neutrophil Gelatinase-associated Lipocalin as a Marker of Postoperative Acute Kidney Injury Following Cardiac Surgery in Patients with Preoperative Kidney Impairment.

INTRODUCTION: Acute kidney injury (AKI) is a serious complication of cardiac surgery. The current 'gold standard' for determining AKI is change in serum creatinine and urine output, however, this change occurs relatively late after the actual injury occurs. Identification of new biomarkers that detect early AKI is required. Recently, new biomarkers, such as the NephroCheck® Test and AKIRisk have also been tested and found to be good indicators of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in paediatric patients but has displayed varied results in adult populations, particularly post cardiac surgery. The aim of this study was to assess the value of urinary NGAL as a biomarker of AKI in patients with pre-existing renal impairment (eGFR >15ml/min to eGFR<60ml/min). METHODS: A post-hoc analysis of urinary NGAL concentrations from 125 patients with pre-existing kidney impairment, who participated in a randomised trial of haemofiltration during cardiac surgery, was undertaken. Urinary NGAL was measured using ELISA at baseline, post-operatively and 24 and 48 hours after surgery, and serum creatinine was measured pre and postoperatively and then at 24, 48, 72 and 96 hours as routine patient care. NGAL concentrations were compared in patients with and without AKI determined by changes in serum creatinine concentrations. A Kaplan-Meier plot compared survival for patients with or without AKI and a Cox proportional hazards analysis was performed to identify factors with the greatest influence on survival. RESULTS: Following surgery, 43% of patients developed AKI (based on KDIGO definition). Baseline urinary NGAL was not found to be significantly different between patients that did and did not develop AKI. Urinary NGAL concentration was increased in all patients following surgery, regardless of whether they developed AKI and was also significant between groups at 24 (p=0.003) and 48 hours (p<0.0001). Urinary NGAL concentrations at 48 hours correlated with serum creatinine concentrations at 48 hours (r=0.477, p<0.0001), 72 hours (r=0.488, p<0.0001) and 96 hours (r=0.463, p<0.0001). Urinary NGAL at 48 hours after surgery strongly predicted AKI (AUC=0.76; P=0.0001). A Kaplan- Meier plot showed that patients with postoperative AKI had a significantly lower 7-year survival compared with those without AKI. Postoperative urinary NGAL at 48 hours >156ng/mL also strongly predicted 7-year survival. However, additive EuroSCORE, age, current smoking and post-operative antibiotics usage were distinctly significantly more predictive of 7-year survival as compared with postoperative urinary NGAL at 48 hours >156ng/mL. CONCLUSIONS: Our study demonstrated that postoperative urinary NGAL levels at 48 hours postsurgery strongly predicts the onset or severity of postoperative AKI based on KDIGO classification in patients with preoperative kidney impairment and were also strongly related to 7-year survival.

The impact of continuous haemofiltration with high-volume fluid exchange during cardiopulmonary bypass surgery on the recovery of patients with impaired renal function: a pilot randomised trial.

BACKGROUND: There is widespread variability in clinical practice within cardiac surgery units worldwide on the use of haemofiltration. The clinical impact and safety of this modality is, however, unknown. OBJECTIVES: The primary pilot trial objectives were as follows: to assess the feasibility of randomising 60 patients with impaired kidney function undergoing on-pump coronary artery bypass graft (CABG) surgery within 6 months; to assess the suitability and reliability of our chosen outcome measures; to explore issues that may impact on recruitment into a definitive trial; and to undertake an exploratory economic evaluation. DESIGN: A pilot, single-centre, open-label randomised trial. SETTING: Liverpool Heart and Chest Hospital NHS Foundation Trust between November 2010 and March 2012. PARTICIPANTS: Men and women, aged > 18 years of age, undergoing on-pump CABG surgery, who had pre-operative impaired kidney function indicated by an estimated glomerular filtration rate (eGFR) of < 60 ml/minute adjusted for 1.73 m(2) of body surface area. INTERVENTIONS: Group 1: patients who received haemofiltration during bypass (experimental group). Group 2: patients who did not receive haemofiltration during bypass (control group). MAIN OUTCOME MEASURES: (1) Feasibility outcome measures: barriers to recruitment to a larger trial were documented as observations made during the recruitment period of the trial. Reliability of data collection methods was monitored using a 13-point case record form validation check for data entry against the patient clinical notes and the trial database. (2) The main clinical outcomes were frequency of intensive care unit (ICU) stay of duration > 3 days and the length of ICU stay days. (3) Other clinical outcomes were the need for postoperative haemofiltration in the ICU, mechanical ventilation time, hospital stay, composite of outcome of unfavourable perioperative events and eGFR values at 6 weeks' follow-up. (4) Secondary health economic feasibility outcomes. RESULTS: Recruitment into the pilot trial was from 21 November 2010 to 30 March 2012. Thirty-seven eligible patients were consented and successfully randomised into the trial arms (30%). The main issues impacting on recruitment were the high volume of off-pump CABG surgery within the centre; recruitment being restricted to research nurses' working hours of the week; issues arising associated with the screening process for identifying prospective eligible patients based on eGFR values; protocol deviations/treatment crossovers; and unexpected outbreaks of pandemic influenza and other infectious conditions. The data collection process was sufficiently robust, with few errors detected. The length of ICU stay days was deemed a suitable primary outcome. There was an overall trend towards reduction in the length of ICU stay for patients who were given intraoperative haemofiltration, more so for those with diabetes. The economic evaluation estimated that the incremental costs per person were £1744 lower for the intraoperative haemofiltration group, while the incremental benefits per person increased by 0.11. CONCLUSION: Given sufficient resources and broadening of the inclusion criteria, the recruitment into a larger multicentre trial is feasible and may demonstrate potential clinical and cost benefits of using intraoperative haemofiltration in this group of patients. However, owing to the small sample size in this pilot trial, no firm conclusions can be drawn from the findings at this stage. The outcomes of this pilot study are very encouraging and suggest that it is feasible to design a continuous superiority trial with the length of ICU stay days or time to tracheal extubation as the primary outcome measure, provided that guidelines for avoiding bias are implemented. An alternative primary outcome measure that avoids bias is mortality. The inclusion criteria should also be widened to include all cardiac surgery patients with impaired renal function. TRIAL REGISTRATION: ISRCTN49513454. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 49. See the HTA programme website for further project information.

The influence of leaflet skin friction and stiffness on the performance of bioprosthetic aortic valves.

Leaflet skin friction and stiffness were found to have a significant influence on the systolic performance of a 19 mm diameter bioprosthetic aortic valve based on fluid-structure interaction simulations at a heart rate of 72 bpm. Four different leaflet skin friction coefficients (0.0, 9.2 × 10(-4), 4.8 × 10(-2) and 4.8 × 10(-1)) were simulated along with three different leaflet elastic moduli (3.0 × 10(6), 3.5 × 10(6), 4.0 × 10(6) N m(-2)). Higher leaflet skin friction was found to increase the magnitude of the systolic transvalvular pressure gradient and the peak velocity through the valve, as well as decrease the valve orifice area. The results for the leaflet opening and closing kinematics also showed that higher leaflet skin friction combined with higher leaflet stiffness produces longer rapid valve opening, closing and ejection times, as well as smaller valve orifice areas. These results are consistent with clinical findings for calcified aortic valves and suggest that valve performance under stenotic conditions is strongly influenced by the combined effect of increasing leaflet stiffness and surface roughness caused by calcification.

Experimental validation of the fluid-structure interaction simulation of a bioprosthetic aortic heart valve.

Experiments performed on a 19 mm diameter bioprosthetic valve were used to successfully validate the fluid-structure interaction (FSI) simulation of an aortic valve at 72 bpm. The FSI simulation was initialized via a novel approach utilizing a Doppler sonogram of the experimentally tested valve. Using this approach very close quantitative agreement (≤12.5%) between the numerical predictions and experimental values for several key valve performance parameters, including the peak systolic transvalvular pressure gradient, rapid valve opening time and rapid valve closing time, was obtained. The predicted valve leaflet kinematics during opening and closing were also in good agreement with the experimental measurements.

A pilot randomised controlled trial in intensive care patients comparing 7 days' treatment with empirical antibiotics with 2 days' treatment for hospital-acquired infection of unknown origin.

BACKGROUND: Management of cardiac intensive care unit (ICU) sepsis is complicated by the high incidence of systemic inflammatory response syndrome, which mimics sepsis but without an infective cause. This pilot randomised trial investigated whether or not, in the ICU, 48 hours of broad-spectrum antibiotic treatment was adequate to safely treat suspected sepsis of unknown and unproven origin and also the predictive power of newer biomarkers of sepsis. OBJECTIVE: The main objective of this pilot study was to provide preliminary data on the likely safety and efficacy of a reduced course of antibiotics for the treatment of ICU infections of unknown origin. DESIGN: A pilot, single-centre, open-label randomised trial. SETTING: This study was carried out in the ICU of a tertiary heart and chest hospital. PARTICIPANTS: Patients being treated within the ICU were recruited into the trial if the intensivist was planning to commence antibiotics because of evidence of systemic inflammatory response syndrome and a strong suspicion of infection but there was no actual known source for that infection. INTERVENTIONS: Broad-spectrum antibiotic treatment administered for 48 hours (experimental) compared with treatment for 7 days (control). MAIN OUTCOME MEASURES: The primary outcome was a composite outcome of the rate of death or initiation of antibiotic therapy after the completion of the treatment schedule allocated at randomisation. Secondary outcomes included the duration of mechanical ventilation and ICU and hospital stay; the incidence of infection with Clostridium difficile (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008, or methicillin-resistant Staphylococcus aureus (MRSA) (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008; resource utilisation and costs associated with each of the two pilot arms; the ratio of patients screened to patients eligible to patients randomised; the incidence of crossover between groups; and the significance of newer biomarkers for sepsis for predicting patients' need for further antibiotics. RESULTS: A total of 46 patients were recruited into the trial, with 23 randomised to each group. There was no significant difference between the two groups in terms of the composite primary outcome measure. The risk difference was 0.12 [95% confidence interval (CI) 0.11 to 0.13; p = 0.3]. In the 2-day group, four patients (17.4%) required further antibiotics compared with three (13%) in the 7-day group. Four patients died within the trial period and the deaths were not trial related. Patients who died during the trial period received no additional antibiotics in excess of their trial allocation. There were no documented incidences of MRSA or C. difficile infection in either group. No significant differences in adverse events were observed between the groups. Key economic findings were mean antibiotic costs per patient of £168.97 for the 2-day group and £375.86 for the 7-day group. The potential per annum cost saving for the ICU of 2-day treatment was estimated to range from £108,140 to £126,060. Patient screening was considered the biggest barrier to recruitment. There was no crossover between the two randomised groups. Data verification ascertained > 98% accuracy in data collection. Baseline procalcitonin was found to be predictive of the composite outcome (death and needing further antibiotics) (odds ratio 1.79, 95% CI 1.20 to 2.67; p = 0.005). Analysis of baseline procalcitonin also indicated a trend towards it being a predictor of restarting antibiotics, with an odds ratio of 1.45 (95% CI 1.04 to 2.02; p = 0.01). CONCLUSIONS: Data from this pilot study suggest that there could be significant benefits of reducing broad-spectrum antibiotic use in the ICU without it undermining patient safety, with a potential cost saving in our unit of over £100,000 per year. Evidence from this pilot trial is not definitive but warrants further investigation using a large randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82694288. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 36. See the HTA programme website for further project information.

Maternal influenza in the etiology of schizophrenia.

There are epidemiological reasons for suspecting that infections may contribute to the etiology of schizophrenia, and it is claimed that the birth cohort that was in utero during the 1957 influenza epidemic in Helsinki, Finland, now has an increased incidence of schizophrenia. Three studies, all based on the admission statistics of Scottish psychiatric hospitals, were therefore undertaken to determine whether those who were in utero during the influenza A epidemics of 1918 to 1919 and 1957 were subsequently at increased risk of schizophrenia. Edinburgh data suggest that those who were in the sixth month of intrauterine development during the 1957 epidemic were subsequently at increased risk, but Scottish national data do not reveal any increased risk associated with either the 1918 to 1919 or 1957 epidemics. Overall, the hypothesis that maternal influenza may contribute to the etiology of schizophrenia is not supported, but the possibility cannot yet be discounted.

Winter-born v summer-born schizophrenics.

Data from two sources--the Edinburgh Psychiatric Case Register and the psychiatric inpatient records of the Scottish Health Service--were used to compare large populations of first-admission schizophrenics born in winter (January to March) and in summer (June to October). Parallel comparisons were carried out for affective psychoses. Comparison of the months of birth of the Scottish patients with those of the general population indicated that there was a 9% excess of schizophrenic births and a 3% excess of affective births in the first 3 months of the year. In the Edinburgh material, winter-born schizophrenics were more likely than the summer-born to receive a diagnosis of paranoid or schizoaffective schizophrenia and less likely to receive diagnoses other than schizophrenia on readmission, but neither of these differences emerged in the much larger Scottish material. There were no differences between winter- and summer-born schizophrenics in age of onset, sex ratio, or prognosis in either data set, nor were any significant differences found between winter- and summer-born affectives. We have therefore failed to demonstrate any convincing differences between winter- and summer-born schizophrenics.

Is the incidence of renal carcinoma increasing?

An analysis of standardised incidence rates for renal parenchymal tumours over a 14-year period in Scotland demonstrated a significant increase in disease incidence for males but not females. Reasons are presented to support the contention that this increase is in part real.

Cancer of the prostate. Do younger men have a poorer survival rate?

Analysis of cancer registration survival data, together with a review of published clinical and pathological studies, strongly suggests that cancer of the prostate occurring before the age of 55 has a worse survival prospect than at ages up to 74. The likely reasons appear to be a higher degree of malignancy of tumours in younger men and, particularly, late diagnosis from failure to suspect the disease in this age group. This suggests that routine clinical examination of the prostate should be carried out as soon as feasible after the age of 40.